In this combined phase I/II, open label, single arm trial to study, the safety and efficacy of combination Golcadomide and nivolumab in patients with non-Hodgkin lymphoma (NHL) who have experienced refractory/residual disease, at or after 30 days of receiving chimeric antigen T-cell (CAR-T) therapy will be studied. A dose escalation phase will be followed by a dose expansion design.
Non-Hodgkin lymphoma (NHL) is a diverse group of lymphoid neoplasms affecting 80,470 new cases in the USA every year.1 Among the common types of NHL, diffuse large B-cell lymphoma (DLBCL) carries a five-year survival of 64.4% (SEER). Prognosis depends on disease specific factors such as stage and extent of spread, in addition to patient specific factors, such as age and performance status. Prior studies suggest that anti-PD-1 therapy may be effective in this population, especially if there is a way to further sensitize tumor cells to anti-PD-1 therapy to reduce T-cell exhaustion and increase inflammatory cytokines. Exposure to CELMoDs in addition to anti-PD1 therapy following CAR-T relapse may lead to deeper and more durable responses through re-expansion of CAR-T cells and modulation of tumor microenvironment (TME). This trial hypothesizes that combination Golcadomide at the selected dose and nivolumab at standard dosing will be safe and effective and that an overall response rate 45% or greater with a maximum dose-limiting toxicity (DLT) rate of 25% would be sufficient to warrant further interest in this combination in patients who have refractory NHL after 30 days of receiving therapy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Golcadomide (GOLCA, CC-99282) is an oral cereblon E3 ligase modulator (CELMoD®) agent with immunomodulatory and tumor cell-autonomous activities. It is a modulator of the E3 ubiquitin ligase complex containing cereblon (CRL4-CRBN E3 ubiquitin ligase), with potential immunomodulating and antineoplastic activities.
Nivolumab is an immune checkpoint inhibitor targeted therapy drug that blocks the PD-1 (programmed death receptor-1) pathway to help prevent cancer cells from hiding from the immune system, boosting the immune system's response.
Maximum tolerated dose (MTD) / Recommended Phase 2 dose (RP2D)
The number and type of Dose Limiting Toxicities experienced during the first two cycles of treatment will be observed and assessed (per NCI-CTCAE v5.0) to determine the Maximum tolerated dose (MTD) / recommended phase 2 dose (RP2D) of golcadomide combined with standard dose nivolumab in participants with NHL who experienced disease progression or relapse after receiving CAR-T therapy as determined.
Time frame: Up to 56 days from start of treatment
Lugano Response Evaluation
Occurrence of partial response or better (objective response) per the Lugano PET-CT treatment response criteria. The Lugano classification (2014) is a lymphoma staging system that includes response based on CT evaluation. Scoring: (1)=no uptake or no residual uptake (when used interim), (2)=slight uptake, but below blood pool (mediastinum), (3)=uptake above mediastinal, but below or equal to uptake in the liver, (4)=uptake slightly to moderately higher than liver, (5)=markedly increased uptake or any new lesion (on response evaluation). Complete metabolic response (CMR) (score of 1, 2 or 3 in nodal or extranodal sites with or without a residual mass. Partial metabolic response (PMR) (score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size), or stable disease or no metabolic response (score of 4 or 5 with no obvious change in FDG uptake)
Time frame: Up to 36 months
Adverse Events and Serious Adverse Events (Phase l - Dose Escalation)
Incidence of severity of adverse events and serious adverse events at least possibly related to trial treatment, per NCI-CTCAE v5.0.
Time frame: Up to 56 days from start of treatment
Adverse Events and Serious Adverse Events (Phase ll - Dose Expansion)
Incidence of severity of adverse events and serious adverse events at least possibly related to trial treatment, per NCI-CTCAE v5.0.
Time frame: Up to 36 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Preliminary Efficacy per Lugano Response Evaluation
Occurrence of partial response or better (objective response) per the Lugano PET-CT treatment response criteria. The Lugano classification (2014) is a lymphoma staging system that includes response based on CT evaluation. Scoring: (1)=no uptake or no residual uptake (when used interim), (2)=slight uptake, but below blood pool (mediastinum), (3)=uptake above mediastinal, but below or equal to uptake in the liver, (4)=uptake slightly to moderately higher than liver, (5)=markedly increased uptake or any new lesion (on response evaluation). Complete metabolic response (CMR) (score of 1, 2 or 3 in nodal or extranodal sites with or without a residual mass. Partial metabolic response (PMR) (score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size), or stable disease or no metabolic response (score of 4 or 5 with no obvious change in FDG uptake)
Time frame: Up to 26 months
Progression-free survival (PFS)
Median time patients do not experience disease progression per Lugano classification (2014). Lugano criteria is a staging system including CT response evaluation. Scoring: (1)=no uptake or no residual uptake (when used interim),(2)=slight uptake, but below blood pool (mediastinum),(3)=uptake above mediastinal, but below or equal to uptake in the liver,(4)=uptake slightly to moderately higher than liver,(5)=markedly increased uptake or any new lesion (on response evaluation). Disease progression score=4 or 5 in any lesion with an increase in intensity of FDG uptake from baseline (and/or new FDG-avid foci consistent with lymphoma). Complete metabolic response (CMR) (score=1, 2 or 3 in nodal or extranodal sites with or without a residual mass, partial metabolic response (PMR) (score= 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size), or stable disease or no metabolic response (score=4 or 5 with no obvious change in FDG uptake)
Time frame: Up to 36 months